Abstract

Although the specific causes of colorectal cancer (CRC) are not known, a robust DNA repair capacity may decrease the risk of this malignancy. DNA repair capacity may be reduced by alterations of genes involved in DNA repair process. This may affect susceptibility to carcinogenesis. It is hypothesized that single nucleotide polymorphisms (SNPs) of several DNA repair genes may be a risk factor for CRC susceptibility and prognosis. Using PCR–RFLP method, we conducted a case-control study to genotype 291 patients with CRC and 140 healthy individuals to determine variants in the PRKDC, XPD and XRCC1 genes. Results showed that the genotypes of XRCC1 c.580C>T polymorphism were associated with the risk of CRC. Compared with CC, CT (odds ratio (OR) = 5.35, P < 0.001) and CT/TT (OR = 4.74, P < 0.001) as well as T allele (OR = 4.95, P < 0.001) were overrepresented among the CRC patients. Variant genotype CC (OR = 2.37; P = 0.042) and C allele of XPD c.2251A>C (OR = 1.37; P = 0.028) polymorphism, enhanced the risk of CRC cases. Compared with GG, positive association was also obtained for all genotypes (GT, TT, GT/TT) of PRKDC rs7003908; 6721G>T polymorphism with CRC. Moreover, T allele of PRKDC demonstrated significant risk for CRC (OR = 5.61; P < 0.001). Besides, significant relevance of the PRKDC rs7003908; 6721G>T variations to smoking as well as XPD c.2251A>C variations to smoking and alcohol consumption in individuals with CRC was observed. Our findings indicated that genetic polymorphisms of PRKDC, XRCC1, XPD genes may influence susceptibility of CRC in the Iranian population.

中文翻译：

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三种DNA修复基因（PRKDC，XPD，XRCC1）的遗传多态性与大肠癌易感性有关

摘要

尽管尚不知道结直肠癌（CRC）的具体原因，但强大的DNA修复能力可能会降低这种恶性肿瘤的风险。DNA修复能力可能会因涉及DNA修复过程的基因改变而降低。这可能会影响致癌性。假设几个DNA修复基因的单核苷酸多态性（SNP）可能是CRC易感性和预后的危险因素。使用PCR-RFLP方法，我们对291名CRC患者和140名健康个体的基因型进行了病例对照研究，以确定PRKDC，XPD和XRCC1基因的变异。结果表明，XRCC1的基因型c.580C> T多态性与CRC风险有关。与CC相比，CRC中CT（奇数比（OR）= 5.35，P <0.001）和CT / TT（OR = 4.74，P <0.001）以及T等位基因（OR = 4.95，P <0.001）过多耐心。XPD c.2251A> C的变异基因型CC（OR = 2.37; P = 0.042）和C等位基因（OR = 1.37; P = 0.028）多态性增加了CRC病例的风险。与GG相比，PRKDC rs7003908的所有基因型（GT，TT，GT / TT）也获得了正相关。具有CRC的6721G> T多态性。此外，PRKDC的T等位基因显示出明显的CRC风险（OR = 5.61；P<0.001）。此外，PRKDC rs7003908具有重要意义；在CRC患者中，观察到6721G> T对吸烟的变化以及XPD c.2251A> C对吸烟和饮酒的变化。我们的发现表明，PRKDC，XRCC1，XPD基因的遗传多态性可能影响伊朗人群中CRC的易感性。